This project will investigate the disturbances of immunoregulation that are associated with experimental disseminated histoplasmosis (D-HPL) in the mouse, and similar studies will be conducted on patients with D-HPS. Our laboratory has demonstrated potent immunosuppressor activity by spleen cells from mice with D-HPL on the immune response of normal splenocytes measured by primary antibody formation in vitro and cell-mediated cytotoxic activity. The specific cell or cells mediating suppression will be identified; putative suppressor T cells will be estimated by a system of selective lysis with anti-Ly serum plus complement. Reversal of suppressor activity during infection will be attempted by adult thymectomy, cyclophosphamide administration and injection with antiserum to the I-J subregion of the H-2 histocompatibility complex. The immunoregulatory function of blood mononuclear cells from patients with D-HPL will be studied by cell mixing experiments wherein the relative suppressor activity of freshly isolated cells as well as cells pre-incubated with or without concanavalin A will be studied. Certain well-characterized T-cell subclasses in blood will be labeled by an indirect fluorescent antibody technique and quantitated in a fluorescence-activated cell sorter to determine if imbalances of these subclasses occur in D-HPL.